The objective of this program is to support basic research on the developmental aspects of brain, and to investigate metabolic causes of mental retardation. The biochemical influence of hyperaminoacidemias on brain development and certain enzyme activities related to amino acid metabolism will be investigated in rats and pregnant sheep. In patients with amino acidopathies and fibroblasts obtained from skin tissue cultures, defects such as sarcosinemia, ketotic and non-ketotic hyperglycinemia and different forms of branched chain ketoaciduria will be studied. Specific important compounds of the brain will be analyzed during development, including brain subcellular fractions; a calcium- binding protein from brain has been isolated and characterized. An extensive study is made of patients and tissue cultures of patients with different kinds of mucopolysaccharide and lipid storage diseases. An animal model of beta-galactosidase deficiency is being developed, as is a GLC method for the analysis of mucopolysaccharides in urine.